Methadone and Phenobarbital Interaction
Drug interaction information between Methadone and Phenobarbital.
Methadone and Phenobarbital have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Methadone and Phenobarbital. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
Both drugs slow down the central nervous system, and taking them together makes this effect much stronger. This can lead to dangerous breathing problems, extreme sleepiness, or even death.
FDA Label Information
John’s Wort, Phenobarbital Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death (see WARNINGS ).
Methadone Also Interacts With
- Itraconazole major
- Safinamide major
- Tranylcypromine moderate
- Gabapentin minor
- Sertraline minor
Phenobarbital Also Interacts With
- Nirmatrelvir/Ritonavir major
- Ranolazine major
- Voriconazole major
- Canagliflozin moderate
- Cenobamate moderate
Frequently Asked Questions
What SPL severity band is on file for Methadone + Phenobarbital?
Compiled FDA labeling labels this pair moderate. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Phenobarbital has 59 labeled pairs on file vs Methadone's 41. In the moderate band specifically: Methadone has 2 (also Tranylcypromine); Phenobarbital has 13 (also Canagliflozin, Cenobamate, Clarithromycin, Dapsone Topical).
What mechanism field is on file for Methadone and Phenobarbital?
Both drugs slow down the central nervous system, and taking them together makes this effect much stronger. This can lead to dangerous breathing problems, extreme sleepiness, or even death.
Phenobarbital carries more major-labeled pairs than Methadone
SPL source-record counts only. This page's band is moderate · classes on file: Methadone (Opioid Agonist); Phenobarbital (Anticonvulsant (Barbiturate)).
Phenobarbital has 3 major-labeled pairs vs Methadone's 2. This page itself is in the moderate band, not the major band.
2 major · 2 moderate · 37 minor · 41 total
- Other moderate peers for Methadone
- Tranylcypromine
3 major · 13 moderate · 43 minor · 59 total
- Other moderate peers for Phenobarbital
- Canagliflozin
- Cenobamate
- Clarithromycin
- Dapsone Topical
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.